Fig. 5: KDM3A-catalysed acetyl-hydroxylation links roles of 2-oxoglutarate oxygenases in the hypoxic response and histone modifications.
From: KDM3A catalyses the oxidation of acetyl-lysine to hydroxyacetyl-lysine on histone H3K9
KDM3A is a JmjC KDM acting on H3K9me1/2 and, as shown here, hydroxylates H3K9ac. KDM3A activity regulates HIF-αβ-enabled expression and KDM3A is a HIF target gene, so KDM3A levels rise in hypoxia. The JmjC subfamily 2OG oxygenase FIH catalyses HIF-α Asn-hydroxylation, causing reduced interaction of αβ-HIF with the histone acetyltransferases CBP/p300, so decreasing HIF-αβ promotes transcription. Catalysis by the HIF-α prolyl-hydroxylases (PHD1–3), which are not JmjC subfamily 2OG oxygenases, signals for HIF-α degradation in an O2-availability-limited manner. 2OG oxygenase reactions are shown in red, each of which is coupled to conversion of O2/2OG to succinate/CO2.
